Biologists Create Wiring Diagram Of Cell Division

The study, published January 25 in the open access journal PLoS Computational Biology, looks at the molecular machinery that governs replication of DNA and cell division in Caulobacter crescentus, an easily studied bacterium that is closely related to the bacteria that fix nitrogen in legumes and to the bacteria that cause brucellosis in cattle and Rocky Mountain spotted fever in humans.

“All share the same characteristic of asymmetric division; the daughter cells are different than the mother cell in some fashion,” explains co-author John Tyson. “In C. crescentus, the mother cell attaches to a rock by a sticky stalk. If there is good eating, she divides and creates a daughter that can swim away. The stalked cell remains attached to the rock and the daughter—with a flagellum instead of a stalk—swims away, so that it does not compete with mama. After about 35 to 40 minutes, the daughter loses the flagellum, grows a stalk, and settles down to become a mother.”

The researchers are interested in the molecular machinery that governs replication of DNA and division of a cell into two different cell types. “A lot is known about genes that control this process,” said Tyson. “The mechanism is very complicated, involving dozens of genes and even more proteins. From experimental observations it is possible to construct a hypothetical ‘wiring diagram’ of how these genes and proteins interact.”

But it is difficult to predict how cells will control their replication-division cycles from such a complicated hypothesis, he said. They have converted the wiring diagram into “mathematical equations that can be solved on a computer so that we can say with more confidence how the mechanism will govern cell growth, division, and differentiation.”

For example, models can be used to make testable predictions. A basic experiment is to create a mutant bacterium by knocking out a gene – thus learning the role of the gene. This mutation can be simulated in the mathematical model to confirm the role of the gene in the wiring diagram.

CITATION: Li S, Brazhnik P, Sobral B, Tyson JJ (2008) A quantitative study of the division cycle of Caulobacter crescentus stalked cells. PLoS Comput Biol 4(1): e9. doi:10.1371/journal.pcbi.0040009